• Male Gender is independently associated with pulmonary tuberculosis among sputum and non-sputum producers people with presumptive tuberculosis in Southwestern Uganda

      Boum, Y; Atwine, D; Orikiriza, P; Assimwe, J; Page, A-L; Mwanga-Amumpaire, J; Bonnet, M (BioMed Central, 2014-12-10)
      BackgroundLittle is known about the association between gender and risk of TB infection. We sought to assess the impact of gender on TB prevalence among people with presumptive tuberculosis at a regional referral hospital in a high TB and HIV prevalence setting.MethodsWe analyzed data from two diagnostic TB studies conducted in rural, southwestern Uganda. People with presumptive tuberculosis were evaluated by chest X-ray, fluorescence microscopy, TB culture, and HIV testing. Our primary outcome of interest was TB infection, as defined by a positive TB culture. Our primary explanatory variable of interest was gender. We fit univariable and multivariable logistic regression models to investigate associations between TB infection and gender, before and after adjusting or possible confounding factors, including ability to produce sputum, age and residence.ResultsBetween April 2010 and September 2012, 863 people with presumptive tuberculosis (PWPTB) were enrolled in the two studies at Mbarara Regional Referral Hospital (MRRH) in Uganda. Among them 664 (76.9%) were able to produce sputum. X-ray was suggestive of TB for 258 (66.5%) of males and 175 (44.8%) of female (p¿<¿0.001). using microscopy 84 (20%) of males and 48 (10.9%) of females were diagnosed with TB (p¿<¿0.001) while 122 (30.3%) of males and 76 (18.4%) of females were diagnosed with TB (p¿<¿0.001) using TB culture.In multivariable logistic regression models, the odds of having TB was higher in males than females (AOR 2.2 (1.56-3.18 95%CI°, P¿<¿0.001), after adjustment for age, HIV status, ability to produce sputum, and residence.ConclusionIn Southwestern Uganda, TB prevalence is higher among male than female people with presumptive TB. The increased risk of TB among males is independent of other TB risk factors. These findings emphasize the need for gender-focused interventions aimed at reducing TB transmission.
    • MDR tuberculosis and non-compliance with therapy (correspondence)

      Cox, H; Hughes, J; Ford, N; London, L; Medecins Sans Frontieres (Elsevier, 2012-03)
    • MDR tuberculosis and non-compliance with therapy.

      Cox, H; Hughes, J; Ford, N; London, L; Médecins Sans Frontières, Khayelitsha, Cape Town, South Africa; and University of Cape Town, Cape Town, South Africa (Elservier, 2012-03)
    • A misleading appearance of a common disease: tuberculosis with generalized lymphadenopathy—a case report

      Bottineau, MC; Kouevi, KA; Chauvet, E; Garcia, DM; Galetto-Lacour, A; Wagner, N (Oxford University Press, 2019-09-28)
      Introduction: Tuberculosis is a common illness for vulnerable populations in resource-limited settings. Lymph nodes in tuberculosis represent the most frequent extra-pulmonary form of tuberculosis in children, but lymph nodes are rarely generalized and large. We report an atypical pediatric case of tuberculosis with lymphadenopathy. Patient concerns and findings: A two-year-old child with severe acute malnutrition presented with painless, generalized, and excessively large nodes which were not compressive and were without fistula. Main diagnoses, interventions, outcomes: Fine needle aspiration was performed and led to the detection of lymph node granulomatous lymphadenitis suggestive of tuberculosis. Conclusion: The child was immediately initiated on anti-tuberculosis therapy with a very successful outcome. Clinicians should be aware of atypical manifestations such as the one we describe in the interest of swift diagnosis and initiation of treatment.
    • Missed Opportunities for Earlier Diagnosis of rifampicin-resistant Tuberculosis despite access to Xpert(®) MTB/RIF

      Mohr, E; Daniels, J; Muller, O; Furin, J; Chabalala, B; Steele, S J; Cox, V; Dolby, T; Ferlazzo, G; Shroufi, A; et al. (International Union Against Tuberculosis and Lung Disease, 2017-10-01)
      To assess the proportion of rifampicin-resistant tuberculosis (RR-TB) patients with potential earlier RR-TB diagnoses in Khayelitsha, South Africa.
    • Model of care and risk factors for poor outcomes in patients on multi-drug resistant tuberculosis treatment at two facilities in eSwatini (formerly Swaziland), 2011–2013

      Verdecchia, M; Keus, K; Blankley, S; Vambe, D; Ssonko, C; Piening, T; Casas, EC (Public Library of Science, 2018-10-17)
    • Modelling the Effect of Short-Course Multidrug-Resistant Tuberculosis Treatment in Karakalpakstan, Uzbekistan

      Trauer, JM; Achar, J; Parpieva, N; Khamraev, A; Denholm, JT; Falzon, D; Jaramillo, E; Mesic, A; du Cros, P; McBryde, ES (BioMed Central, 2016-11-18)
      Multidrug-resistant tuberculosis (MDR-TB) is a major threat to global TB control. MDR-TB treatment regimens typically have a high pill burden, last 20 months or more and often lead to unsatisfactory outcomes. A 9-11 month regimen with seven antibiotics has shown high success rates among selected MDR-TB patients in different settings and is conditionally recommended by the World Health Organization.
    • Moderate to severe malnutrition in patients with tuberculosis is a risk factor associated with early death.

      Zachariah, R; Spielmann M P; Harries, A D; Salaniponi, F M L; Médecins Sans Frontières-Luxembourg, Thyolo District, Malawi. zachariah@internet.lu (Elsevier, 2008-02-07)
      A study was conducted in new patients registered with tuberculosis (TB) in a rural district of Malawi to determine (i) the prevalence of malnutrition on admission and (ii) the association between malnutrition and early mortality (defined as death within the first 4 weeks of treatment). There were 1181 patients with TB (576 men and 605 women), whose overall rate of infection with human immunodeficiency virus (HIV) was 80%. 673 TB patients (57%) were malnourished on admission (body mass index [BMI] < 18.5 kg/m2). There were 259 patients (22%) with mild malnutrition (BMI 17.0-18.4 kg/m2), 168 (14%) with moderate malnutrition (BMI 16.0-16.9 kg/m2) and 246 (21%) with severe malnutrition (BMI < 15.9 kg/m2). 95 patients (8%) died during the first 4 weeks. Significant risk factors for early mortality included increasing degrees of malnutrition, age > 35 years, and HIV seropositivity. Among all the 1181 patients, 10.9% of the 414 patients with moderate to severe malnutrition died in the first 4 weeks compared with 6.5% of the 767 patients with normal to mild malnutrition (odds ratio 1.8, 95% confidence interval 1.1-2.7). In patients with TB, BMI < 17.0 kg/m2 is associated with an increased risk of early death.
    • Moxifloxacin for tuberculosis - Authors' reply.

      Cox, H; Ford, N; von Schoen-Angerer, T; Médecins Sans Frontières, Khayelitsha, Cape Town, South Africa; University of Cape Town, Cape Town, South Africa; Médecins Sans Frontières Campaign for Access to Essential Medicines, Geneva, Switzerland (Elsevier, 2012-03)
    • The Multi-Drug Resistant Tuberculosis Diagnosis and Treatment Cascade in Bangladesh

      Hossain, S T; Isaakidis, P; Sagili, K D; Islam, S; Islam, M A; Shewade, H D; Kamal, S M M; Husain, A (Public Library of Science, 2015-06-25)
      To determine, in areas supported by BRAC, Bangladesh i) the pre-diagnosis and pre-treatment attrition among presumptive and confirmed Multi-Drug Resistant Tuberculosis (MDR-TB) patients and ii) factors associated with attrition.
    • Multidisease testing for HIV and TB using the GeneXpert platform: A feasibility study in rural Zimbabwe

      Ndlovu, Z; Fajardo, E; Mbofana, E; Maparo, T; Garone, D; Metcalf, C; Bygrave, H; Kao, K; Zinyowera, S (Public Library of Science, 2018-03-02)
      HIV Viral Load and Early Infant Diagnosis technologies in many high burden settings are restricted to centralized laboratory testing, leading to long result turnaround times and patient attrition. GeneXpert (Cepheid, CA, USA) is a polyvalent near point-of-care platform and is widely implemented for Xpert MTB/RIF diagnosis. This study sought to evaluate the operational feasibility of integrated HIV VL, EID and MTB/RIF testing in new GeneXpert platforms.
    • Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

      Ahuja, S D; Ashkin, D; Avendano, M; Banerjee, R; Bauer, M; Bayona, J N; Becerra, M C; Benedetti, A; Burgos, M; Centis, R; et al. (2012-08)
      Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB.
    • Multidrug- and isoniazid-resistant tuberculosis in three high HIV burden African regions

      Sanchez-Padilla, E; Ardizzoni, E; Sauvageot, D; Ahoua, L; Martin, A; Varaine, F; Adatu-Engwau, F; Akeche, G; Salaniponi, F; Bonnet, M (International Union Against Tuberculosis and Lung Disease, 2013-08)
      Despite major progress in the surveillance of drug-resistant tuberculosis (TB), data are lacking for many low-resource countries. World Health Organization estimates of multidrug-resistant TB (MDR-TB) rates in Africa are low, and based on very limited data from the African continent.
    • Multidrug-Resistant Tuberculosis in Central Asia.

      Cox, H; Orozco, J D; Male, R; Ruesch-Gerdes, S; Falzon, D; Small, I; Doshetov, D; Kebede, Y; Aziz, M; Médecins Sans Frontières Aral Sea Area Programme, Uzbekistan and Turkmenistan, Tashkent, Uzbekistan. hom@msfh-tashkent.uz (2004-05)
      Multidrug-resistant tuberculosis (MDR-TB) has emerged as a major threat to TB control, particularly in the former Soviet Union. To determine levels of drug resistance within a directly observed treatment strategy (DOTS) program supported by Médecins Sans Frontières in two regions in Uzbekistan and Turkmenistan, Central Asia, we conducted a cross-sectional survey of smear-positive TB patients in selected districts of Karakalpakstan (Uzbekistan) and Dashoguz (Turkmenistan). High levels of MDR-TB were found in both regions. In Karakalpakstan, 14 (13%) of 106 new patients were infected with MDR-TB; 43 (40%) of 107 previously treated patients were similarly infected. The proportions for Dashoguz were 4% (4/105 patients) and 18% (18/98 patients), respectively. Overall, 27% of patients with positive smear results whose infections were treated through the DOTS program in Karakalpakstan and 11% of similar patients in Dashoguz were infected with multidrug-resistant strains of TB on admission. These results show the need for concerted action by the international community to contain transmission and reduce the effects of MDR-TB.
    • Multidrug-Resistant Tuberculosis Treatment Failure Detection Depends on Monitoring Interval and Microbiological Method

      Mitnick, CD; White, RA; Lu, C; Rodriguez, CA; Bayona, J; Becerra, MC; Burgos, M; Centis, R; Cohen, T; Cox, H; et al. (European Respiratory Society, 2016-09-01)
      Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.
    • Multidrug-resistant tuberculosis treatment outcomes in Karakalpakstan, Uzbekistan: treatment complexity and XDR-TB among treatment failures.

      Cox, H; Kalon, S; Allamuratova, S; Sizaire, V; Tigay, Z; Rüsch-Gerdes, S; Karimovich, H; Kebede, Y; Mills, C; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia. (PLoS, 2007)
      BACKGROUND: A pilot programme to treat multidrug-resistant TB (MDR-TB) was implemented in Karakalpakstan, Uzbekistan in 2003. This region has particularly high levels of MDR-TB, with 13% and 40% among new and previously treated cases, respectively. METHODOLOGY: This study describes the treatment process and outcomes for the first cohort of patients enrolled in the programme, between October 2003 and January 2005. Confirmed MDR-TB cases were treated with an individualised, second-line drug regimen based on drug susceptibility test results, while suspected MDR-TB cases were treated with a standardised regimen pending susceptibility results. PRINCIPAL FINDINGS: Of 108 MDR-TB patients, 87 were started on treatment during the study period. Of these, 33 (38%) were infected with strains resistant to at least one second-line drug at baseline, but none had initial ofloxacin resistance. Treatment was successful for 54 (62%) patients, with 13 (15%) dying during treatment, 12 (14%) defaulting and 8 (8%) failing treatment. Poor clinical condition and baseline second-line resistance contributed to treatment failure or death. Treatment regimens were changed in 71 (82%) patients due to severe adverse events or drug resistance. Adverse events were most commonly attributed to cycloserine, ethionamide and p-aminosalicylic acid. Extensively drug resistant TB (XDR-TB) was found among 4 of the 6 patients who failed treatment and were still alive in November 2006. CONCLUSIONS: While acceptable treatment success was achieved, the complexity of treatment and the development of XDR-TB among treatment failures are important issues to be addressed when considering scaling up MDR-TB treatment.
    • Multidrug-resistant tuberculosis.

      Nyang'wa, BT; Berry, C; Fielding, K; Nunn, AJ (Elsevier, 2019-07-27)
    • "My Favourite Day Is Sunday": Community Perceptions of (Drug-Resistant) Tuberculosis and Ambulatory Tuberculosis Care in Kara Suu District, Osh Province, Kyrgyzstan

      Burtscher, D; Van den Bergh, R; Toktosunov, U; Angmo, N; Samieva, N; Rocillo Arechaga, E P (Public Library of Science, 2016-03-28)
      Kyrgyzstan is one of the 27 high multidrug-resistant tuberculosis (MDR-TB) burden countries listed by the WHO. In 2012, Médecins Sans Frontières (MSF) started a drug-resistant tuberculosis (DR-TB) project in Kara Suu District. A qualitative study was undertaken to understand the perception of TB and DR-TB in order to improve the effectiveness and acceptance of the MSF intervention and to support advocacy strategies for an ambulatory model of care.
    • Mycobacterium Tuberculosis Lineage 4 Comprises Globally Distributed and Geographically Restricted Sublineages

      Stucki, D; Brites, D; Jeljeli, L; Coscolla, M; Liu, Q; Trauner, A; Fenner, L; Rutaihwa, L; Borrell, S; Luo, T; et al. (Nature Publishing Group, 2016-12-01)
      Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.
    • The Need to Accelerate Access to New Drugs for Multidrug-resistant Tuberculosis

      Cox, H; Furin, J J; Mitnick, C D; Daniels, C; Cox, V; Goemaere, E (World Health Organization, 2015-07-01)
      Approximately half a million people are thought to develop multidrug-resistant tuberculosis annually. Barely 20% of these people currently receive recommended treatment and only about 10% are successfully treated. Poor access to treatment is probably driving the current epidemic, via ongoing transmission. Treatment scale-up is hampered by current treatment regimens, which are lengthy, expensive, poorly tolerated and difficult to administer in the settings where most patients reside. Although new drugs provide an opportunity to improve treatment regimens, current and planned clinical trials hold little promise for developing regimens that will facilitate prompt treatment scale-up. In this article we argue that clinical trials, while necessary, should be complemented by timely, large-scale, operational research that will provide programmatic data on the use of new drugs and regimens while simultaneously improving access to life-saving treatment. Perceived risks - such as the rapid development of resistance to new drugs - need to be balanced against the high levels of mortality and transmission that will otherwise persist. Doubling access to treatment and increasing treatment success could save approximately a million lives over the next decade.